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1.
Open Vet J ; 14(1): 256-265, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38633181

RESUMEN

Background: Milk is considered one of the most important capital goods and essential sources of animal protein in the diet of the Egyptian family, as well as an effective means to improve the economic condition of farmers, considering this important view, the policymakers need accurate and advance information regarding future supply for planning on the both short and long term. Aim: The study aims to forecast the production of milk in Egypt during the period from 2022 to 2025 using the Autoregressive Integrated Moving Average (ARIMA) model using time series data of milk production (MP) (1970-2021) obtained from the Central Agency for public mobilization and statistics (CAPMS). Methods: Augmented Dickey-Fullar Unit Root test, Partial autocorrelation function (PACF), and Autocorrelation function (ACF) of the time series sequence were used to judge the stationarity of the data. After confirming the stationarity of the data, the appropriate ARIMA model was selected based on certain statistical parameters like significant coefficients, values of adjusted R-squared, Akaike information criteria (AIC), Schwarz criterion (SC), and Standard Error of Regression. After the selection of the model based on the previous parameters, the verification of the model was employed by checking the residuals of the Correlogram-Q-Statistics test. Results: The most fitted model to predict the future levels of MP in Egypt was ARIMA (1, 1, and 3). Conclusion: Using the ARIMA (1, 1, 3) model, it could be forecasted that the production of milk in Egypt would show an increasing trend from 6,152.606 thousand tons in 2022 to 6,360.829 thousand tons in 2025.


Asunto(s)
Leche , Modelos Estadísticos , Animales , Egipto , Incidencia , Factores de Tiempo
2.
Orthop Rev (Pavia) ; 16: 116370, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666190

RESUMEN

Background Following surgical treatment of ankle fractures, geriatric patients face high complication rates (CR) in literature. Commonly used diagnostic and treatment algorithms fail to consider requirements of ageing patients which increases the risk of postoperative complications. Objective Present study critically evaluated surgical management of ankle fractures in patients over 65 years old, with focus on identifying modifiable risk factors and effective comorbidity management strategies. Methods We conducted a retrospective single-center study on patients who underwent surgical treatment of an ankle fracture. Based on their age, participants were divided into non-geriatric patients (NGP<65y) and geriatric patients (GP≥65y). We analyzed overall CR and number of minor and major complications in relation to timing of surgery, biological sex, injury pattern, osteosynthesis, pre-existing medical conditions, and postoperative care. Results 402 patients were included. GP encountered significantly higher overall (p<0.001), minor (p<0.001) and major (p=0.003) complications. They presented more complex, displaced and open fractures. Predominant factor contributing to higher CR in NGP and markedly in GP was concomitant diseases, presenting a strong OR of 19,290 (p<0.001) and 17,022 (p<0.001). Delaying surgery and managing comorbidities preoperatively had a favorable impact. Conclusion We revealed a high significant correlation between pre-existing medical conditions and postoperative results. To ascertain viability of delayed surgery in facilitating additional diagnostics and treatment of comorbidities, further comparative trials with a larger cohort are imperative.

3.
Int J Antimicrob Agents ; 63(6): 107164, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38574873

RESUMEN

OBJECTIVE: Multiple strategies have been utilised to reduce the incidence of HIV, including PrEP and rapid antiretroviral therapy initiation. The study objectives were to evaluate the efficacy, safety, satisfaction, treatment adherence, and system retention obtained with rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in naïve patients. METHODS: This phase IV, multicenter, open-label, single-arm, 48-week clinical trial enrolled patients between January 2020 and June 2022. Adherence to treatment was evaluated with the SMAQ questionnaire and patient satisfaction with the EQ-5D. RESULTS: Two hundred eight participants were enrolled with mean age of 35.6 years; 87.6% were males; mean CD4 count was 393.5 cells/uL (<200 cells/uL in 22.1%); viral load log was 5.6 (VL>100 000 cop/mL in 43.3%); 22.6% had AIDS, and 4.3% were coinfected with HBV. BIC/FTC/TAF was initiated on the day of their first visit to the HIV specialist in 98.6% of participants, and 9.6% were lost to follow-up. The efficacy at week 48 was 84.1 % by intention-to- treat (ITT), 94.6% by modified ITT, and 98.3% by per protocol analysis. The regimen was discontinued in two subjects (0.9%) during week 1 for grade 3 adverse events. Treatment adherence (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95%; P = 0.49]) and patient satisfaction (weeks 4 [90%, IQR: 80-99%] vs. 48 [90%, IQR: 80-95 P = 0.49]) rates were very high over the 48- week study period. CONCLUSIONS: BIC/FTC/TAF is an appropriate option for rapid ART initiation in naïve HIV patients, offering high efficacy, safety, durability, treatment adherence, retention in the healthcare system, and patient satisfaction. Number Clinical Trial registration: NCT06177574.

4.
Clin Case Rep ; 12(4): e8560, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38550744

RESUMEN

Key Clinical Message: A unique ER/PR-positive mucinous adenocarcinoma of breast but CK7/CK20 negativity. A rare finding of Lymphoplasmacytic Infiltration is noted. Successful treatment included modified radical mastectomy and tamoxifen-based therapy, leads to remission. Abstract: Mucinous carcinoma, which is characterized by the presence of abundant extracellular mucin, is a rare and distinctive subtype of invasive breast cancer. This subtype accounts for less than 5% of all invasive breast cancers, with pure mucinous carcinoma representing only around 2%. It is most commonly found in older patients, typically in the sixth to early eighth decade of life. We present the case of a 55-year-old female with a 15-year history of a painless, gradually enlarging palpable lump on her left breast. Upon examination, a 5 × 5 cm lump with well-defined margins and a hard consistency was found in the lower outer quadrant of the left breast. Histopathological examination confirmed a diagnosis of Mucinous Adenocarcinoma of the Left Breast. The patient underwent modified radical mastectomy and received adjuvant endocrine therapy with tamoxifen due to hormone receptor-positive status. Mucinous carcinoma of the breast is a unique entity with specific histological features including the presence of extracellular mucin pools. Immunohistochemical staining is crucial for determining hormone receptor status, which can guide treatment decisions. Although surgical intervention is the primary approach, the extent of surgery may vary, ranging from lumpectomy to mastectomy. Adjuvant therapies such as chemotherapy and radiotherapy may also be considered based on individual cases. This case underscores the importance of a multidisciplinary approach in managing rare subtypes of breast cancer, such as mucinous carcinoma. Accurate diagnosis, appropriate surgical intervention, adjuvant therapy, and long-term follow-up are critical components of treatment.

5.
PLoS One ; 19(3): e0300737, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38551917

RESUMEN

BACKGROUND: There is ample evidence supporting the use of different manipulative therapy techniques for Cervicogenic Headache (CgH). However, no technique can be singled as the best available treatment for patients with CgH. Therefore, the objective of the study is to find and compare the clinical effects of cervical spine over thoracic spine manipulation and conventional physiotherapy in patients with CgH. DESIGN, SETTING, AND PARTICIPANTS: It is a prospective, randomized controlled study conducted between July 2020 and January 2023 at the University hospital. N = 96 eligible patients with CgH were selected based on selection criteria and they were divided into cervical spine manipulation (CSM; n = 32), thoracic spine manipulation (TSM; n = 32) and conventional physiotherapy (CPT; n = 32) groups, and received the respective treatment for four weeks. Primary (CgH frequency) and secondary CgH pain intensity, CgH disability, neck pain frequency, neck pain intensity, neck pain threshold, cervical flexion rotation test (CFRT), neck disability index (NDI) and quality of life (QoL) scores were measured. The effects of treatment at various intervals were analyzed using a 3 × 4 linear mixed model analysis (LMM), with treatment group (cervical spine manipulation, thoracic spine manipulation, and conventional physiotherapy) and time intervals (baseline, 4 weeks, 8 weeks, and 6 months), and the statistical significance level was set at P < 0.05. RESULTS: The reports of the CSM, TSM and CPT groups were compared between the groups. Four weeks following treatment CSM group showed more significant changes in primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, neck pain frequency, pain intensity, pain threshold, CFRT, NDI and QoL) than the TSM and CPT groups (p = 0.001). The same gradual improvement was seen in the CSM group when compared to TSM and CPT groups (p = 0.001) in the above variables at 8 weeks and 6 months follow-up. CONCLUSION: The reports of the current randomized clinical study found that CSM resulted in significantly better improvements in pain parameters (intensity, frequency and threshold) functional disability and quality of life in patients with CgH than thoracic spine manipulation and conventional physiotherapy. TRIAL REGISTRATION: Clinical trial registration: CTRI/2020/06/026092 trial was registered prospectively on 24/06/2020.


Asunto(s)
Manipulación Espinal , Cefalea Postraumática , Humanos , Dolor de Cuello/terapia , Calidad de Vida , Cefalea Postraumática/terapia , Estudios Prospectivos , Vértebras Torácicas , Manipulación Espinal/métodos , Vértebras Cervicales , Rango del Movimiento Articular , Resultado del Tratamiento
6.
Mar Pollut Bull ; 201: 116264, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38492266

RESUMEN

Plastic debris accumulating on beaches pose a major threat to marine ecosystems. Unexpected events affecting human operations, such as the COVID-19 pandemic, which prompted governments to implement safety measures and restrictions, can serve as an unplanned investigation of anthropogenic pressure on the marine environment. This study aimed to explore deviations in macroplastic delivery rates to the central eastern Red Sea shoreline during three distinct population mobility periods: before, during, and after COVID-19 restrictions, spanning from January 2019 to June 2022. We observed a 50 % reduction in the estimated macroplastic delivery rates during the lockdown, followed by a 25 % increase after restrictions were eased. Seasonal variations in delivery rates were also observed, with higher values during the winter monsoon. Reduced shoreline litter delivery during the pandemic highlights human operations as a cause of macroplastic litter and suggests the potential of temporary measures to reduce plastic pollution in the coastal environment.


Asunto(s)
COVID-19 , Residuos , Humanos , Residuos/análisis , Ecosistema , Océano Índico , Pandemias , Monitoreo del Ambiente , Plásticos , Playas , Control de Enfermedades Transmisibles
7.
Viruses ; 16(2)2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38400035

RESUMEN

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Oxazinas , Piperazinas , Piridonas , Humanos , Persona de Mediana Edad , Lamivudine/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , España , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Antirretrovirales/uso terapéutico , Lípidos
8.
Health Sci Rep ; 7(2): e1379, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38299209

RESUMEN

Introduction: Out-of-hospital cardiac arrest (OHCA) is defined as the loss of functional mechanical activity of the heart in association with an absence of systemic circulation, occurring outside of a hospital. Immediate coronary angiography (CAG) with percutaneous coronary intervention is recommended for OHCA with ST-elevation. We aimed to evaluate the effect of early CAG on mortality and neurological outcomes in OHCA patients without ST-elevation. Methods: This meta-analysis and systemic review was conducted as per principles of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) group. A protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, Ref No. = CRD42022327833). A total of 674 studies were retrieved after scanning several databases (PubMed Central, EMBASE, Medline, and Cochrane Central Register of Controlled Trials). Results: A total of 18 studies were selected for the final analysis, including 6 randomized control trials and 12 observational studies. Statistically, there was no significant difference in primary outcome, i.e., mortality, between early and delayed CAG. In terms of the grade of neurological recovery as a secondary outcome, early and delayed CAG groups also showed no statistically significant difference. Conclusion: Early CAG has no survival benefits in patients with no ST elevations on ECG after OHCA.

9.
Heliyon ; 10(4): e26593, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38420493

RESUMEN

This paper presents the first assessment of marine litter in the Mogadishu coastal area of Somalia. Samples were collected monthly using 100 m × 40 m transect and classified following OSPAR Marine Litter Survey Guide while litter sources were identified using Ocean Conservancy Marine Debris Index. The results showed a total of 119873 items consisting of plastics (89.47%), clothing items (7.53%), and others (3.00%) recovered from Liido Beach. Litter density ranged from 2.19 items/m2 to 14.18 items/m2 with a mean of 6.25 items/m2 and Clean Coast Index (CCI) suggesting that Liido Beach is extremely dirty (>20 items/m2). In addition, the primary sources of marine litter at the beach are local recreational and shoreline activities (54.12%), and dumping (36.61%). The dominance of plastic litter on the beach poses potential threats to marine biodiversity in the Somalia coastal area and the West Indian Ocean. It is recommended that effective strategies and solutions to mitigate litter on the beach and other coastal areas in Somalia should be developed and compensated with public education and awareness campaigns across the country.

11.
Mol Cancer Res ; 22(4): 347-359, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38284821

RESUMEN

IMPLICATIONS: Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.


Asunto(s)
Aprendizaje Profundo , Neoplasias de la Próstata , Masculino , Humanos , Proteínas de Fusión Oncogénica/genética , Neoplasias de la Próstata/patología , Prostatectomía , Regulador Transcripcional ERG , Serina Endopeptidasas/genética
13.
BMC Infect Dis ; 24(1): 150, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297213

RESUMEN

BACKGROUND: Bacterial infections are considered a leading cause of hospitalization and death globally. There is still a need for a rapid and feasible biomarker for bacterial infections. Heparin-binding protein (HBP) was shown to be related to bacterial infections. The objective of the study is to investigate the diagnostic accuracy of HBP in bacterial infections. METHODS: Articles were screened in PubMed, SCOPUS, Web of Science, and Cochrane to recognize eligible studies. We included studies investigating the diagnostic accuracy of HBP and reported the necessary data to construct 2 × 2 tables. A univariate analysis was conducted to determine the pooled sensitivity and specificity, and a bivariate diagnostic random-effects model was used to calculate the optimal cut-off point. RESULTS: The analysis comprised sixteen studies in total. Plasma HBP showed a sensitivity of 0.90 (95% CI: [0.79, 0.96]) and a specificity of 0.87 (95% CI: [0.66, 0.96]) in diagnosing bacterial infections using blood samples. Pooling data from seven studies revealed that HBP in cerebrospinal fluid (CSF) has sensitivity and specificity of 96% (95% CI: [0.85, 0.99]), and 95% (95% CI: [0.89, 0.97]), respectively, for the diagnosis of bacterial meningitis. In urinary tract infections (UTI), urine-HBP was revealed to have a high diagnostic value in discriminating bacterial from non-bacterial UTI infection at a cut-off value of 32.868 ng/ml with sensitivity and specificity of 87%. CONCLUSION: HBP has shown a high diagnostic accuracy of bacterial infections, including UTI and meningitis. Further studies are needed to determine its prognostic value and whether it could guide antibiotic therapy.


Asunto(s)
Proteínas Sanguíneas , Meningitis Bacterianas , Infecciones Urinarias , Humanos , Sensibilidad y Especificidad , Infecciones Urinarias/diagnóstico , Péptidos Catiónicos Antimicrobianos , Meningitis Bacterianas/diagnóstico
14.
PLoS One ; 19(1): e0293458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38236912

RESUMEN

BACKGROUND AND OBJECTIVES: The World Health Organization (WHO) declared the coronavirus disease-19 (COVID-19) pandemic on March 11, 2020. The health care system faced tremendous challenges in providing ethical and high-quality care. The impact of COVID-19 on urological practices varied widely worldwide, including in Arab countries. This study aimed to compare the influence of the COVID-19 pandemic on urology practice in Egypt, the KSA, and the UAE during the first year of the pandemic. METHODS: This sub-analysis assessed the demographics and COVID-19's effects on urological practice in terms of adjustments to hospital policy, including outpatient consultations, the management of elective and urgent surgical cases, and the continuation of education across the three countries. The availability of personal protective equipment (PPE) and urologists' emotional, physical, and verbal intimidation during COVID-19 were also compared. RESULTS: Regarding the impact on hospital policy, consultations replaced by telemedicine were significantly higher in the KSA (36.15%), followed by the UAE (33.3%), then Egypt (10.4%) (P = 0.008). Elective cases requiring ICU admission were 65.1% in Egypt, 45.2% in the KSA, and 58.2% in the UAE and were performed only in high-risk patients. PPE was freely available in 20.8% of the Egyptian hospitals compared to 83.3% in the KSA and 81.8% in the UAE. Online courses were significantly higher in Egypt (70.8%), followed by the UAE (53%) and the KSA (41.7%) (P = 0.02). Emotional intimidation was higher than verbal intimidation, representing 80%, 75.9%, and 76% in the UAE, KSA, and Egypt, respectively. CONCLUSION: This sub-analysis outlined significant hospital policy changes across the three Arab countries. Exposure to emotional, verbal, and physical intimidation was observed. The development of teleconsultations and online platforms for educational purposes was observed.


Asunto(s)
COVID-19 , Urología , Humanos , COVID-19/epidemiología , Pandemias , SARS-CoV-2 , Árabes
15.
Nat Commun ; 15(1): 363, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191471

RESUMEN

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.


Asunto(s)
Células Madre Mesenquimatosas , Neoplasias de la Próstata , Humanos , Masculino , Animales , Ratones , Neoplasias de la Próstata/genética , Próstata , Células del Estroma , Diferenciación Celular , Microambiente Tumoral/genética
16.
Ann Thorac Surg ; 117(4): 859-865, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38081497

RESUMEN

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. METHODS: Administrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. RESULTS: A total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. CONCLUSIONS: A minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient's risk of stroke with the increased risk of bleeding, particularly in the postoperative period.


Asunto(s)
Fibrilación Atrial , Procedimientos Quirúrgicos Cardíacos , Accidente Cerebrovascular , Adulto , Humanos , Anticoagulantes/efectos adversos , Warfarina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Hemorragia/inducido químicamente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Administración Oral , Factores de Riesgo
18.
J Endourol ; 38(1): 2-7, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37917100

RESUMEN

Objective: National guidelines recommend periprocedural antibiotics before percutaneous nephrolithotomy (PCNL), yet it is not clear which is superior. We conducted a randomized trial to compare two guideline-recommended antibiotics: ciprofloxacin (cipro) vs cefazolin, on PCNL outcomes, focusing on the development of systemic inflammatory response syndrome (SIRS) criteria. Methods: Adult patients who were not considered high risk for surgical or infectious complications and undergoing PCNL were randomized to receive either cipro or cefazolin perioperatively. All had negative preoperative urine cultures. Demographic and perioperative data were collected, including SIRS criteria, intraoperative urine culture, duration of hospitalization, and need for intensive care. SIRS is defined by ≥2 of the following: body temperature <96.8°F or >100.4°F, heart rate >90 bpm, respiratory rate >20 per minute, and white blood cell count <4000 or >12,000 cells/mm3. Results: One hundred forty-seven patients were enrolled and randomized (79 cefazolin and 68 cipro). All preoperative characteristics were similar (p > 0.05), except for mean age, which was higher in the cipro group (64 vs 57 years, p = 0.03). Intra- and postoperative findings were similar, with no difference between groups (p > 0.05), except a longer mean hospital stay in the cefazolin group (2 hours longer, p = 0.02). There was no difference between SIRS episodes in both univariate and multivariate analyses. Conclusions: Despite the relatively broader coverage for urinary tract pathogens with ciprofloxacin, this prospective randomized trial did not show superiority over cefazolin. Our findings therefore support two appropriate options for perioperative antibiotic prophylaxis in patients undergoing PCNL who are nonhigh risk for infectious complications.


Asunto(s)
Antibacterianos , Cálculos Renales , Nefrolitotomía Percutánea , Complicaciones Posoperatorias , Adulto , Humanos , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Ciprofloxacina/uso terapéutico , Cálculos Renales/cirugía , Nefrolitotomía Percutánea/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Método Simple Ciego , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/etiología
19.
Arch Pharm (Weinheim) ; 357(1): e2300201, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37937360

RESUMEN

Dementia is a cognitive disturbance that is generally correlated with central nervous system diseases, especially Alzheimer's disease. The limited number of medications available is insufficient to improve the lifestyle of the patients suffering from this disease. Thus, new benzimidazole-thiazole hybrids (3-10) were designed and synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory agents. The in vitro evaluation displayed that the derivatives 4b, 4d, 5b, 6a, 7a, and 8b demonstrated dual inhibitory efficiency against both AChE with IC50 ranging from 4.55 to 8.62 µM and BChE with IC50 ranging from 3.50 to 8.32 µM. By analyzing the Lineweaver-Burk plot, an uncompetitive form of inhibition was determined for the highly active compound 4d, revealing its inhibition type. The human telomerase reverse transcriptase-immortalized retinal pigment epithelial cell line was used to ensure the safety of the most potent cholinesterase inhibitors. Furthermore, compounds 4b, 4d, 5b, 6a, 7a, and 8b were evaluated for their neuroprotective and antioxidant properties, as well as their ability to suppress COX-2. The results demonstrated that compounds 4d, 5b, and 8b presented significant neuroprotection efficiency against H2 O2 -induced damage in SH-SY5Y cells with % cell viability of 67.42 ± 7.90%, 62.51 ± 6.71%, and 72.61 ± 8.10%, respectively, while the tested candidates did not reveal significant antioxidant activity. Otherwise, compounds 4b, 6a, 7a, and 8b displayed outstanding COX-2 inhibition effects with IC50 ranging from 0.050 to 0.080 µM relative to celecoxib (IC50 = 0.050 µM). In addition, molecular docking was carried out for the potent benzimidazole-thiazole hybrids with the active sites of both AChE (PDB ID: 4EY7) and BChE (PDB code: 1P0P). The tested candidates fit well in the active sites of both portions, with docking scores ranging from -8.65 to -6.64 kcal/mol (for AChE) and -8.71 to -7.73 kcal/mol (for BChE). In silico results show that the synthesized benzimidazole-thiazole hybrids have good physicochemical and pharmacokinetic properties with no Lipinski rule violations. The preceding results exhibited that compound 4d could be used as a new template for developing more significant cholinesterase inhibitors in the future.


Asunto(s)
Enfermedad de Alzheimer , Neuroblastoma , Humanos , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Tiazoles/farmacología , Ciclooxigenasa 2/metabolismo , Relación Estructura-Actividad , Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Bencimidazoles/farmacología , Estructura Molecular
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